This project study three different neural systems where many of the factors that are thought to limit axonal regeneration in the central nervous system are either minimized or held constant and where the success of axonal regeneration differs. The hypothesis to be tested is that loss of the information necessary to lead a regenerating axon back to its specific denervated synaptic sites may be a primary factor limiting axonal regeneration (loss of specificity). After cutting axons in the amphibian optic nerve, amphibian and newborn rat spinal cord, and amphibian and rat dorsal roots we will compare the success of regeneration with the number of abnormal connections made by regenerating or growing axons when other sites along the course of the regenerating axons are or are not denervated. Methods to be used for tracing the generating axonal connections include the use of anterograde transport of tritiated amino acids followed by a quantitative autoradiographic analysis and cutting regenerated axons and using electron dense synaptic knobs to identify these connections in electron micrographs. Using these systems and methods of analysis we can directly compare the success of regeneration with the amount of non-specificity.